Promising Cancer Drug Target In Prostate Tumors Identified

Scientists at Dana-Farber Cancer Institute report they have blocked the development of prostate tumors in cancer-prone mice by knocking out a molecular unit they described as a "powerhouse" that drives runaway cell growth.

In an article that is being published as an advanced online publication by the journal Nature, the researchers said the growth-stimulating molecule called p110beta – part of a cellular signaling network disrupted in several common cancers – is a promising target for novel cancer therapies designed to shut it down. Lead authors of the report are Shidong Jia, MD, PhD, Zhenning Liu, PhD, Sen Zhang PhD, and Pixu Liu, MD, PhD.

The p110beta molecule and a counterpart, p110alpha, are "isoforms" – slightly different forms – of an enzyme called PI(3)K that is an intense focus of cancer research and drug development. PI(3)K is the linchpin of a cell-signal pathway that responds to growth factor signals from outside the cell.

When activated by growth factor receptors, PI(3)K turns on a cascade of genes and proteins that drives cells to divide and grow. The molecular accelerator is normally kept under control by a tumor-suppressor protein, PTEN, which acts like a brake to curb excess cell growth that could lead to cancer.

Mutations that inactivate PTEN – in effect releasing the brake on growth signals – are found in a significant proportion of prostate, breast and brain tumors. The senior authors of the new report, Jean Zhao, PhD, and Thomas Roberts, PhD, previously showed that blocking p110alpha protein inhibits cancerous growth induced by various cancer-causing proteins, such as Her2 and EGFR. With that knowledge in hand, the researchers, in collaboration with pharmaceutical companies, are developing p110alpha blockers.

P110beta, by contrast, was thought to be a relatively insignificant player in tumors. However, "the surprise in this paper is that p110beta has been found to be a bigger player than p110alpha in tumors that result from PTEN loss," noted Zhao. "Now the drug companies, which have been focusing on p110alpha, will have to think about making p110beta inhibitors as well."

Advertisement

Both forms of the p110 molecule have dual tasks: they are involved in responding to insulin signals – a metabolic function – as well as relaying growth signals from outside the cell. But the importance of 110beta had been vastly underestimated, the researchers said, for reasons they don’t entirely understand.

"We knew that when cells are stimulated with growth factor signals, the activity of p110alpha, but not p110beta, rises rapidly and sharply in triggering excess cell growth," Zhao said. "We speculate that 110beta may be providing a low-level but steady growth stimulus and when PTEN is lost, it becomes an important source of cell proliferation signals."

The new findings stem from experiments in which the scientists disabled the p110beta protein in mice as a way of exploring its normal functions. In one of the experiments, the researchers "knocked out" p110beta in mice that also lacked the PTEN tumor suppressor protein and were therefore highly prone to prostate cancer. Mice that lacked PTEN but had functioning p110beta proteins all developed early prostate cancers by 12 weeks of age. In contrast, the "knockout" mice with no p110beta function remained free of prostate cancer even though the PTEN "brake" had been disabled.

The scientists concluded, as a result, that p110beta becomes a "powerhouse" to drive cancerous cell growth when PTEN function is missing.

In light of the new findings, there is likely to be great interest in finding drugs or other tools to block the p110beta protein in cancers where mutations in PTEN have unleashed the overactive growth signals, said Zhao, who is also an assistant professor of surgery at Harvard Medical School.

The task is made somewhat easier, said Roberts, by the fact that "we know what the inhibitor should look like because of our work on p110alpha inhibitors."

Roberts, who is also a professor of pathology at Harvard Medical School, said that drugs designed to block the p110alpha form are on their way to clinical testing, but he could not predict when p110beta inhibitors might become available for clinical testing.

The research was supported by grants from the National Institutes of Health and the Department of Defense for Cancer Research.

Problems with the prostate gland is fairly common for men over 50, according to webmed. But, developing prostate issues is something that men want to avoid, as the gland plays an important role in male fertility as well as the proper functioning of the urinary tract. An enlarged prostate gland, for example, can block the flow of urine from the bladder causing an urinary tract infection. Mayoclinic suggests that a diet packed with nutrients have a positive impact in prostate health. So, the 5 vegan recipes below will provide all the needed nutrients for optimal prostate gland health.

Where once Epstein Barr Virus and Human Papilloma Virus were believed to affect mostly women, science has found that men can be affected too. Until now, prostate cancer causes have been blamed on genetics. However, older research suggest that the Herpes Viruses have always been suspect as a cause of cancers. More now than ever, Epstein Barr Virus and Human Papilloma Virus are strongly linked to prostate cancer affecting fathers, husbands, brothers, son and fathers.This is relevant given the new focus on prostate cancer, the elusive herpes virus Epstein Barr, and its multitude of transformative symptoms affecting the man in your life.

If you experience symptoms such as frequent urination and poor flow of urine a yearly rectal examination is recommended and may reveal if you have a prostate cancer or an enlarged prostate, suggests Doctor Ademola Orolu, a Family Physician.

The new paradigm for the treatment of prostate cancer from Urology includes drug therapy, surgery and radiation. Researchers say this paradigm holds a good promise for treating previously incurable cancer.

As of April 2017, the U.S. Preventative Services Task Force (USPSTF) reversed its 2012 recommendation to change prostate cancer screening from a D grade (meaning to discourage use of testing) to a C grade or screening based on history and circumstances, in order to improve the screening of men ages 55-69. The task force still does not recommend screening for men age 70 and up.